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Objective: To describe the clinical profile and determine the factors affecting mortality of children admitted with adenovirus infection in a tertiary care centre in South India., Methods: In this observational study, respiratory specimens (nasopharyngeal swab / endotracheal aspirate) were collected from all hospitalized pediatric patients presenting with fever, cough, breathlessness, gastrointestinal symptoms, unexplained encephalopathy or multisystem involvement, between February 2023 and August 2023. Infection with adenovirus was determined by viral pathogen panel based on polymerase chain reaction (PCR) technique. Those referred from elsewhere with positive adenovirus report but non-availability of treatment details and children with coinfections were excluded. The clinical and laboratory profile of children with adenovirus infection were collected and predictors for in-hospital mortality were determined by logistic regression analysis., Results: Out of 527 children who were screened, 130 children with a median (IQR) age of 18 (10, 48) months, had adenovirus infection. 84.5% were aged below 5 years. 62 (41.33%) children required intensive care admission. Abnormal chest radiograph, multisystem involvement and non-respiratory illness were present in 90 (69.2%), 97 (74.62%) and 26 (20%) children. Complications included acute respiratory distress syndrome (n = 8), hemophagocytic lymphohistiocytosis (n = 7), left ventricular dysfunction (n = 11), acute liver cell failure (n = 7), acute kidney injury (n = 13), and multiorgan dysfunction (n = 16). Overall mortality was 13%. Acute kidney injury, left ventricular dysfunction and pancytopenia were identified as factors that may be significantly associated with death., Conclusion: Multisystem involvement was observed in majority of children presenting with adenovirus infection. Non respiratory presentation is seen in a fifth of children with adenovirus infection.

Since their discovery in 1953, research on human adenoviruses (HAdVs) has had diverse foci, resulted in groundbreaking discoveries, such as gene splicing, and generated powerful oncolytic constructs and expression vectors for vaccine development and gene therapy. In contrast, virologists working in this field have made relatively little progress toward the prevention and treatment of the wide spectrum of HAdV-associated diseases. The understanding of species-specific features of viral pathogenesis, or of the mechanisms underlying the establishment of latency and reactivation, is still limited. This group of viruses currently comprises 7 species, 51 serotypes, and 116 unique genotypes. This complexity manifests with a challenging pathophenotypic diversity. Some types are highly virulent, and others do not seem to cause disease in immunocompetent hosts. The assessment of viral load in blood and respiratory specimens has well-acknowledged clinical utility, but the lack of virus typing capabilities easily implementable in clinical laboratories represents a lingering major limitation to the interpretation of positive tests. Some HAdV infections do have severe consequences for both immunocompetent and immunocompromised patients, and the understanding of why this is the case will require more research. Clinical isolates and collections of positive specimens can provide unique resources to investigate the molecular bases of viral virulence and fitness and also help gather information of spatial-temporal patterns of viral circulation in susceptible communities, but they are extremely scarce. Clinical laboratories are underutilized interfaces between patients and academic scientists and have, therefore, a high potential to become valuable collaborators in research moving forward., Competing Interests: The author declares no conflict of interest.

We performed this study to evaluate factors associated with antibiotic prescriptions in children with adenovirus infection, since no studies have attempted to address this aspect in the pediatric population. Retrospective study of children younger than 18 years of age tested positive for adenovirus on a syndromic nasopharyngeal test from 2018 to 2023. We compared the need of pediatric intensive care unit (PICU), invasive ventilation, and other respiratory support, viral etiologies, clinical presentations, imaging, and laboratory results in the precovid (2018-2019) and covid (2020-2022) period. The use of antibiotics was studied with multivariable logistic regression including demographic as well as clinical data as covariates. Two hundred fifty-eight patients were enrolled. One hundred fifty-eight patients received an antibiotic (mean duration 6.2 (±2.7) days (median 4; IQR: 4-7)). Presence of seizures and C-reactive protein values as predictors for antibiotic prescription (OR for seizures: 12.17; 95% CI: 1.42-103.91; p = 0.022; OR for CrP: 1.03; 95% CI: 1.01-1.04; p = 0.001). Seventy-four patients received intravenous antibiotics (74/156, 47.4%). Risk factors for intravenous antibiotic were the presence of decay (OR: 3.74; 95% CI: 1.25-11.71; p = 0.018), CrP values (OR: 1.02; 95% CI: 1.00-1.03; p = 0.001), and presence of seizures (OR: 16.34; 95% CI: 2.65-100.83; p = 0.003). Duration of intravenous antibiotics correlated with the presence of seizures (Coeff: 1.6; 95% CI: 0.41-2.89; p = 0.009) even when adjusted for CrP values.    Conclusion: The clinical presentation of adenovirus infection in children is non-specific, leading to frequent antibiotic prescription despite bacterial co-infections was rare. Higher CrP values and presenting with seizures are significantly associated with a higher risk of receiving antibiotics. Rapid microbiological tests and newer biomarkers can help clinicians to improve antibiotic prescription in this cohort of children. What is Known: • Adenovirus infection is a common cause of fever and respiratory tract infections in children. • Children with adenovirus infections frequently receive antibiotics, but determinants of this practice are poorly established. What is New: • Higher C-reactive protein values and presenting with seizures are significantly associated with antibiotic prescription. • Since the beginning of COVID-19 and implementation of rapid diagnostics, less children with adenovirus infection received antibiotics., (© 2024. The Author(s).)

Competing Interests: The authors have no funding or conflicts of interest to disclose.

Background: Adenovirus infections constitute an important cause of morbidity and mortality after hematopoietic stem cell transplantation. Detection and monitoring of adenovirus in EDTA-plasma by real-time quantitative PCR is a sensitive tool for identification and management of patients at risk of a potentially fatal infection., Objectives: The aim of this study was to evaluate the analytical and clinical performance of the quantitative Adenovirus ELITe MGB® Kit (ELITechGroup S.p.A.) using the ELITe BeGenius® (ELITechGroup S.p.A.) system and compare the assay to a laboratory-developed quantitative real-time PCR assay., Study Design: Analytical sensitivity of the Adenovirus ELITe MGB® Kit was determined by testing serial dilutions of the WHO standard. Detection of adenovirus serotypes was assessed using a panel of 51 serotypes. Clinical sensitivity and specificity were determined by comparing the Adenovirus ELITe MGB® Kit results with the laboratory-developed assay results of 155 retrospective and prospective EDTA-plasma samples from transplant recipients., Results: The analytical sensitivity of the Adenovirus ELITe MGB® Kit was at least 54 (1.7 Log) IU/mL and the quantitative results showed a high correlation with the WHO standard (R 2 = 0.9978; Pearson) within the range of 1.7 to 6.6 Log IU/mL. All 51 adenovirus serotypes were detected. The clinical specificity and sensitivity for EDTA plasma of the Adenovirus ELITe MGB® Kit were 97.4 % and 99.1 % respectively., Conclusion: The Adenovirus ELITe MGB® Kit performed on the ELITe BeGenius® system is a highly sensitive and specific assay for the detection of adenovirus in EDTA-plasma from transplantation patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Human adenoviruses (HAdVs) are common pathogens that are associated with a variety of diseases, including respiratory tract infections (RTIs). Without reliable, fast, and cost-effective detection methods for HAdVs, patients may be misdiagnosed and inappropriately treated. To address this problem, we have developed a multiplex loop-mediated isothermal amplification (LAMP) assay for the detection of the species Human adenovirus B (HAdV-B), Human adenovirus C (HAdV-C) and Human adenovirus E (HAdV-E) that cause RTIs. This multiplexing approach is based on the melting curve analysis of the amplicons with a specific melting temperature for each HAdV species. Without the need for typing of HAdVs, the LAMP results can be visually detected using colorimetric analysis. The assay reliably detects at least 375 copies of HAdV-B and -C and 750 copies of HAdV-E DNA per reaction in less than 35 min at 60 °C. The designed primers have no in silico cross-reactivity with other human respiratory pathogens. Validation on 331 nasal swab samples taken from patients with RTIs showed a 90-94% agreement rate with our in-house multiplex quantitative polymerase chain reaction (qPCR) method. Concordance between the quantitative and visual LAMP was 99%. The novel multiplexed LAMP could be an alternative to PCR for diagnostic purposes, saving personnel and equipment time, or could be used for point-of-care testing.

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose of Review: Lower respiratory tract infections (LRTIs) are an important cause of child morbidity and mortality globally, especially in children under the age of 5 years in Africa. Respiratory viruses, including human adenoviruses (HAdVs), are common causes of LRTIs in children. This review aims to shed light on the epidemiology, clinical manifestations, sequelae, and treatment options specific to adenovirus respiratory infections in African children., Recent Findings: Recent evidence has challenged the perception that adenovirus is a negligible cause of LRTIs. Studies show HAdV emerging as the third most common viral pathogen in fatal pneumonias among under-5 children in low-income and middle-income African countries, contributing to 5.5% of all pneumonia deaths and ranking second in hospital-associated viral pneumonia deaths. Predominant HAdV serotypes associated with disease differ by country and region, and have changed over time. Risk factors for increased disease severity and long-term respiratory sequelae in previously healthy African children with HAdV LRTIs are not well established., Summary: Although respiratory viruses, including HAdV, are recognized contributors to LRTIs, the prevalence and impact of adenovirus infections have been under-recognized and understated. Available data suggests that African children, particularly those under 5 years old, are at risk of severe sequelae from respiratory HAdV infections. Long-term sequelae, including bronchiectasis and postinfectious bronchiolitis obliterans, further underscore the significant impact of HAdV infections. However, the scarcity of comprehensive data hampers our understanding of the extent of the impact of HAdV infections on child lung health in Africa. We recommend scaled-up HAdV surveillance, ensuring its consistent inclusion in population-level LRTI assessments, and expanded and equitable access to diagnostics for early recognition of African children at risk of developing chronic sequelae and death. Enhanced understanding of adenovirus epidemiology and clinical outcomes and the availability of therapeutic options are essential for informed public health strategies and clinical care., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Pediatric allogeneic hematopoietic cell transplant (allo-HCT) recipients are at risk for morbidity and mortality from human adenovirus (HAdV). HAdV can be detected in an asymptomatic state, referred to as infection or with signs or symptoms of illness, referred to as disease. Standardized case definitions are needed to distinguish infection from disease and allow for consistent reporting in both observational cohort studies and therapeutic clinical trials., Methods: A working group of experts in virology, transplant infectious disease, and HCT was assembled to develop HAdV infection and disease definitions with the degree of certainty (i.e., possible, probable, and proven). Definitions were further refined through an iterative process and independently applied by two central review committees (CRCs) to 20 pediatric allo-HCT recipients with at least one HAdV-positive PCR., Results: Initial HAdV infection and disease definitions were developed and updated through an iterative process after reviewing clinical and virological details for 81 subjects with at least one positive HAdV PCR detected in a clinical specimen. Independent application of final definitions to 20 HAdV positive allo-HCT recipients by two CRCs yielded similar number of HAdV infection or disease events but with variation of degree of certainty for some events., Conclusions: Application of definitions by a CRC for a study of HAdV infection and disease is feasible and can provide consistency in the assignment of outcomes. Definitions need further refinement to improve reproducibility and to provide guidance on determining clinical improvement or worsening after initial diagnosis of HAdV infection or disease., (© 2024 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)

Background: Human adenovirus (HAdV) is a common cause of acute respiratory disease (ARD) and has raised significant concerns within the Korean military. Here, we conducted a comprehensive epidemiological analysis of HAdV-associated ARD by evaluating its prevalence, clinical outcomes, and prognosis., Methods: We reviewed data from multiple sources, including the New Defense Medical Information System, Defense Medical Statistical Information System, Ministry of National Defense, Army Headquarters, Navy Headquarters, Air Force Headquarters, and Armed Forces Medical Command. We analyzed data of patients who underwent polymerase chain reaction (PCR) testing for respiratory viruses between January 2013 and July 2022 in all 14 Korean military hospitals. The analysis included the PCR test results, demographic characteristics, health care utilization, and prognosis including types of treatments received, incidence of pneumonia, and mortality., Results: Among the 23,830 individuals who underwent PCR testing at Korean military hospitals, 44.78% (10,670 cases) tested positive for respiratory viruses. Across all military types and ranks, HAdV was the most prevalent virus, with a total of 8,580 patients diagnosed, among HAdV, influenza virus, human metapneumovirus, human parainfluenza virus, and human respiratory syncytial virus. HAdV-infected patients exhibited higher rates of healthcare use compared to non-HAdV-infected patients, including a greater number of emergency visits (1.04 vs. 1.02) and outpatient visits (1.31 vs. 1.27), longer hospitalizations (8.14 days vs. 6.84 days), and extended stays in the intensive care unit (5.21 days vs. 3.38 days). Furthermore, HAdV-infected patients had a higher proportion of pneumonia cases (65.79% vs. 48.33%) and greater likelihood of receiving advanced treatments such as high flow nasal cannula or continuous renal replacement therapy., Conclusion: Our findings indicate that HAdV posed a significant public health concern within the Korean military prior to the coronavirus disease 2019 (COVID-19) pandemic. Given the potential for a resurgence of outbreaks in the post-COVID-19 era, proactive measures, such as education, environmental improvements, and the development of HAdV vaccines, are crucial for effectively preventing future outbreaks., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

We report a middle-childhood girl presented with high-grade fever and headache for 4 days. Following this, the child developed mucocutaneous symptoms. She had a notable family history of autoimmune disease. Tests revealed increased inflammatory markers. On the sixth day of illness, a two-dimensonal echocardiogram showed an enlarged coronary artery, diagnosed as incomplete Kawasaki disease (KD) and treated with IVIG and aspirin.Within a week, her younger sibling, an early-childhood girl presented with features of viral prodrome, developed mucocutaneous lesions and subcutaneous oedema of limbs. Her investigations also showed elevated inflammatory markers and echocardiographic changes, diagnosed as incomplete KD.The subsequent development of KD in siblings, both showing initial viral symptoms and a family history of autoimmune disease, led to the suspicion of a potential viral trigger. This was confirmed through viral PCR studies for human adenovirus (type 3). These cases highlight an unusual occurrence of KD developing in siblings following acute adenoviral infection., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: The circulation of human adenoviruses (HAdV) increased in 2023. In this manuscript, we show that HAdV-B3 was predominant in 2023 in a cohort characterized by the Johns Hopkins Hospital System. We also show that HAdV-B3 was associated with an increase in viral loads in respiratory samples and provide a correlation with the clinical presentations and outcomes., Competing Interests: H.M. has research collaborations with Bio-Rad, Qiagen, and Hologic. H.M. serves on the advisory board for Seegene and as a consultant for BD Diagnostics. H.M. received honoraria from Bio-Rad and BD Diagnostics.

Background: Under the pressure of Human Adenovirus (HAdV)-associated acute respiratory infection (ARI) outbreak in children in Northern Vietnam in the end of 2022, this study was initiated to identify the HAdV subtype(s) and examine the associated clinical features and risk factors of more severe cases., Methods: This study evaluated pediatric patients with ARI which had tested positive for HAdV between October and November 2022 using a multiplex real-time PCR panel. Nasopharyngeal aspirates or nasal swab samples were used for sequencing to identify HAdV subtypes. Clinical data were collected retrospectively., Results: Among 97 successfully sequenced samples, the predominant subtypes were HAdV-B3 (83%), HAdV-B7 (16%) and HAdV-C2 (1%). Lower respiratory manifestations were found in 25% of the patients of which 5% were diagnosed with severe pneumonia. There was no significant association between HAdV subtype and clinical features except higher white blood cell and neutrophil counts in those detected with HAdV-B3 (p<0.001). Co-detection of HAdV with ≥1 other respiratory viruses was found in 13/24(54%) of those with lower respiratory manifestations and 4/5(80%) of those with severe pneumonia (odds ratio (95% confidence interval) vs. those without = 10.74 (2.83, 48.17) and 19.44 (2.12, 492.73) respectively after adjusting for age, sex, birth delivery method, day of disease)., Conclusion: HAdV-B3 and HAdV-B7 were predominant in the outbreak. Co-detection of HAdV together with other respiratory viruses was a strong risk factor for lower respiratory tract illnesses and severe pneumonia. The findings advocate the advantages of multi-factor microbial panels for the diagnosis and prognosis of ARI in children., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Nguyen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: The gastrointestinal (GI) tract is a major human adenovirus (HAdV) replication site in patients undergoing hematopoietic stem cell transplantation (HSCT), yet the prevalence and correlates of HAdV GI infection in this setting have remained poorly recognized, especially among adult HSCT recipients., Design or Methods: We retrospectively studied the prevalence and risk factors of HAdV GI-tissue infection in HSCT recipients (73 adults and 15 children) with GI symptoms who underwent GI-tissue biopsy between January-2012 and December-2017. The presence of HAdV in the GI tissues was determined by real-time PCR., Results: HAdV GI-tissue infection was detected in 21 (23.9%) patients, with similar infection rates identified in adults and children. GI-tissue detection was more common at late (>100 days) compared to early times post-transplantation (50% vs. 12.9%, p < .001). The presence of bloody diarrhea, Arab ethnicity (p = .014) and concurrent cytomegalovirus GI-tissue detection (p = .025) were significantly correlated with HAdV GI-tissue infection, while chronic graft versus host disease was of borderline association (p = .055)., Conclusions: Our findings reveal a high rate and new clinical-demographic correlates of HAdV GI-tissue infection in adult and pediatric HSCT recipients with GI symptoms. The findings highlight the need for future prospective studies to assess the relatedness of HAdV infection to the GI symptoms, and the prevalence, impact, and treatment of HAdV GI infection in HSCT recipients., (© 2023 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Human adenoviruses (HAdVs) constitute a group of ubiquitous viruses that currently comprises 51 well-defined serotypes and more than 113 genotypes classified into seven species, HAdV-A through HAdV-G. The members of these species differ considerably in their genomic characteristics and also in their tropism and pathogenicity. Virus isolation in cell culture remains critical for the preservation and comprehensive characterization of viruses of biomedical interest but has been almost completely abandoned by diagnostic laboratories. Currently, the most frequently used approach for the detection of HAdV in clinical specimens is real-time qPCR targeting a region of the hexon gene, conserved among all genotypes described to the present. In the absence of typing, the detection of an HAdV in association with disease provides limited information. Molecular typing is therefore highly desirable and required in the epidemiological investigation of HAdV-associated disease. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Virus isolation from plasma and whole blood Alternate Protocol 1: Virus isolation from stool Alternate Protocol 2: Virus isolation from respiratory specimens and urine Alternate Protocol 3: Virus isolation from tissue specimens Support Protocol: Inoculation of shell vials Basic Protocol 2: Extraction of highly pure viral genomic DNA from infected cells Basic Protocol 3: Molecular detection of human adenovirus by real-time PCR Basic Protocol 4: Molecular typing for basic identification of species and hexon type Basic Protocol 5: Typing human adenoviruses by next-generation whole-genome sequencing and analysis., (© 2023 Wiley Periodicals LLC.)

Human adenoviruses (HAdVs) are double-stranded DNA viruses that can cause a wide spectrum of disease, including respiratory infections. Little is known about the value of respiratory HAdV quantification and its correlation with disease severity. In this study, we developed a quantitative HAdV droplet digital PCR (ddPCR) assay to study the association between viral loads, circulating types, and clinical outcomes. Remnant respiratory specimens positive for HAdV after the standard of care testing were collected from December 2020 to April 2022. A total of 129 samples were tested by a ddPCR method. Typing was performed using Nanopore sequencing of the hexon gene hypervariable region. Clinical chart reviews were performed to correlate the viral loads with the disease severity. The ddPCR assay showed an analytical sensitivity and a lower limit of quantification below 100 copies/mL. Of 129 positive clinical samples, 100 were quantified by ddPCR, 7 were too concentrated to be quantified, and 22 were negative. Of the 22 false negatives, only 3 were successfully typed; however, 99 of the 107 positive samples had a characterized genotype. The main HAdV types identified in this cohort were C1 (49.5%) followed by C2 (34.3%). No significant difference in HAdV loads was noted between patients who were admitted, those who required supplemental oxygen, and outpatients or between different HAdV types. HAdV ddPCR is a reliable absolute quantification approach for HAdV from respiratory samples. HAdV loads at initial presentation does not appear to differ between patients who require hospitalization versus outpatients. IMPORTANCE Measuring viral load using droplet digital PCR (ddPCR) is an absolute quantification approach that can facilitate comparability between different laboratories. This approach could prove valuable in studies that focus on the clinical utility of quantification. In this study, we evaluate a human adenovirus (HAdV) ddPCR assay and study the relationship between viral loads and outcomes after HAdV respiratory infections., Competing Interests: The authors declare a conflict of interest. H.M. received CME honorarium from Roche. H.M. has research collaborations with BioRad, Roche, and Hologic.

Viruses account for 80% of all cases of acute conjunctivitis and adenovirus; enterovirus and herpes virus are the common causative agents. In general, viral conjunctivitis spreads easily. Therefore, to control the spread, it is crucial to quickly diagnose illnesses, strictly implement hand washing laws, and sanitize surfaces. Swelling of the lid margin and ciliary injection are subjective symptoms, and eye discharge is frequently serofibrinous. Preauricular lymph node swelling can occasionally occur. Approximately 80% of cases of viral conjunctivitis are caused by adenoviruses. Adenoviral conjunctivitis may become a big global concern and may cause a pandemic. Diagnosis of herpes simplex viral conjunctivitis is crucial for using corticosteroid eye solution as a treatment for adenovirus conjunctivitis. Although specific treatments are not always accessible, early diagnosis of viral conjunctivitis may help to alleviate short-term symptoms and avoid long-term consequences.

Background: Human adenovirus (HAdV) is a major pathogen that causes acute respiratory tract infections (ARTI) and is frequently associated with outbreaks. The HAdV prevalence and the predominant types responsible for ARTI outbreaks remains obscure in China., Methods: A systematic review was performed to retrieve literature that reported outbreaks or etiological surveillance of HAdV among ARTI patients in China from 2009 to 2020. Patient information was extracted from the literature to explore the epidemiological characteristics and clinical manifestations of the infection of various HAdV types. The study is registered with PROSPERO, CRD42022303015., Results: A total of 950 articles (91 about outbreaks and 859 about etiological surveillance) meeting the selection criteria were included. Predominant HAdV types from etiological surveillance studies differed from those in outbreak events. Among 859 hospital-based etiological surveillance studies, positive detection rates of HAdV-3 (32.73%) and HAdV-7 (27.48%) were significantly higher than other virus types. While nearly half (45.71%) of outbreaks were caused by HAdV-7 with an overall attack rate of 22.32% among the 70 outbreaks for which the HAdVs were typed by the meta-analysis. Military camp and school were main outbreak settings with significantly different seasonal pattern and attack rate, where HAdV-55 and HAdV-7 were identified as the leading type, respectively. Clinical manifestations mainly depended on the HAdV types and patient's age. HAdV-55 infection tends to develop into pneumonia with poorer prognosis, especially in children <5 years old., Conclusions: This study improves the understanding of epidemiological and clinical features of HAdV infections and outbreaks with different virus types, and helps to inform future surveillance and control efforts in different settings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Human adenovirus (HAdV) is an important viral agent in children which can lead to severe acute respiratory infection (SARI). Reports on molecular epidemiology of HAdVs in Iran are limited. This case-control study is conducted to compare the HAdV infection rate and molecular epidemiology among two groups of children with and without respiratory symptoms in Tehran, Iran during 2018-2019., Methods: Nested PCR was performed on 120 oropharyngeal swabs taken from children aged five and younger with SARI who were hospitalized as the case group, and 120 oropharyngeal swabs were collected from children of the same age without respiratory symptoms as the control group. For positive samples Sanger sequencing was done and a phylogenetic tree was drawn afterward., Results: Out of 120 cases, 8 (6.6%) tested positive for eachHAdV types including 6 (75%) HAdV-B7, 1 (12.5%) HAdV-C2, and 1 (12.5%) HAdV-C6. Among the control group, out of 120 samples, 8 (6.6%) were positive comprising 5 (62.5%) HAdV-C5, 2 (25%) HAdV-F41, and 1 (12.5%) HAdV-C6., Conclusion: The present study indicated a different viewpoint of HAdV molecular epidemiology in which the genotypes were compared in children with and without respiratory symptoms. HAdV prevalence was equally common in cases and controls but different genotypes were detected in these two groups. HAdV-B7 was the main type among children with SARI, dissimilar to children with no respiratory symptoms where HAdV-C5 was the predominant type. Detecting HAdV-F in oropharyngeal swabs was a rare finding, which requires further investigation., (© 2022. The Author(s).)

Adenoviruses are highly prevalent pathogens responsible for a wide range of clinical diseases, including respiratory tract infection, acute gastroenteritis, and conjunctivitis. However, adenovirus infection is rarely associated with central nervous system involvement. Here, we report a fatal viral sepsis and encephalitis in a child caused by a human adenovirus type 7 infection. We detected human adenovirus type 7 in the patient's nasopharyngeal swab, blood, and cerebrospinal fluid. Our findings indicate clinicians should be aware of the possible central nervous system involvement in adenovirus infection., (© 2022. The Author(s).)

Clinical Relevance: This study identifies key signs and symptoms of acute conjunctivitis, that when combined with a point-of-care test, can improve clinician accuracy of diagnosing adenoviral conjunctivitis., Background: Adenoviral conjunctivitis is a common ocular infection with the potential for high economic impact due to widespread outbreaks and subsequent furloughs from work and school. In this report, we describe clinical signs and participant-reported symptoms that most accurately identify polymerase chain reaction (PCR)-confirmed adenoviral conjunctivitis., Methods: Adults with 'red eye' symptoms of four days or less were enrolled. Participants rated 10 ocular symptoms from 0 (not bothersome) to 10 (very bothersome), and indicated the presence or absence of systemic flu-like symptoms. Clinicians determined the presence or absence of swollen lymph nodes and rated the severity of eight ocular signs using a 5-point scale. An immunoassay targeting adenovirus antigen was utilised for the point-of-care test, and conjunctival swab samples were obtained for subsequent adenovirus detection by PCR analyses. Univariate and multivariate logistic regression models were used to identify symptoms and signs associated with PCR-confirmed adenoviral conjunctivitis. The diagnostic accuracy of these clinical findings, and the potential benefit of incorporating point-of-care test results, was assessed by calculating areas under the receiver operating characteristic curves (AUC)., Results: Clinician-rated bulbar conjunctival redness, participant-rated eyelid swelling and overall ocular discomfort had the best predictive value in the multivariate logistic regression model with an AUC of 0.83. The addition of the point-of-care test results to these three clinical sign/symptom scores improved diagnostic accuracy, increasing the AUC to 0.94., Conclusions: Conjunctival redness severity and participant-reported eyelid swelling and overall discomfort, along with adenoviral point-of-care test results, were highly predictive in identifying individuals with PCR-confirmed adenoviral conjunctivitis. Improved diagnostic accuracy by clinicians at the initial presenting visit could prevent unnecessary work furloughs and facilitate earlier treatment decisions.

Background: Human adenoviruses typically cause self-limited respiratory, gastrointestinal, and conjunctival infections in healthy children. In late 2021 and early 2022, several previously healthy children were identified with acute hepatitis and human adenovirus viremia., Methods: We used International Classification of Diseases, 10th Revision , codes to identify all children (<18 years of age) with hepatitis who were admitted to Children's of Alabama hospital between October 1, 2021, and February 28, 2022; those with acute hepatitis who also tested positive for human adenovirus by whole-blood quantitative polymerase chain reaction (PCR) were included in our case series. Demographic, clinical, laboratory, and treatment data were obtained from medical records. Residual blood specimens were sent for diagnostic confirmation and human adenovirus typing., Results: A total of 15 children were identified with acute hepatitis - 6 (40%) who had hepatitis with an identified cause and 9 (60%) who had hepatitis without a known cause. Eight (89%) of the patients with hepatitis of unknown cause tested positive for human adenovirus. These 8 patients plus 1 additional patient referred to this facility for follow-up were included in this case series (median age, 2 years 11 months; age range, 1 year 1 month to 6 years 5 months). Liver biopsies indicated mild-to-moderate active hepatitis in 6 children, some with and some without cholestasis, but did not show evidence of human adenovirus on immunohistochemical examination or electron microscopy. PCR testing of liver tissue for human adenovirus was positive in 3 children (50%). Sequencing of specimens from 5 children showed three distinct human adenovirus type 41 hexon variants. Two children underwent liver transplantation; all the others recovered with supportive care., Conclusions: Human adenovirus viremia was present in the majority of children with acute hepatitis of unknown cause admitted to Children's of Alabama from October 1, 2021, to February 28, 2022, but whether human adenovirus was causative remains unclear. Sequencing results suggest that if human adenovirus was causative, this was not an outbreak driven by a single strain. (Funded in part by the Centers for Disease Control and Prevention.)., (Copyright © 2022 Massachusetts Medical Society.)

Background: Outbreaks of severe, acute hepatitis among children have recently attracted global attention. The pathogen causing the outbreak remains unknown, but there is growing evidence that it may be associated with human adenovirus (HAdV)., Data Sources: A review of adenovirus-related clinical studies, epidemiological studies, etiological studies, and case reports was conducted by reviewers independently., Results: HAdV can cause a wide variety of clinical symptoms. In the Mainland of China, HAdV infection accounts for 5.8%-13% of patients with acute respiratory infections, and these infections are mainly caused by species B, C, and E of HAdV. For acute conjunctivitis, 39.8%-74.9% of sporadic cases were infected by B and D species of HAdV. Outbreaks of keratoconjunctivitis and pharyngoconjunctival fever related to HAdV infection could be found throughout the country. In pediatric patients with acute gastroenteritis, HAdV-41 was the predominant HAdV type, followed by HAdV species B and C. Several types of HAdV, including HAdV-5, HAdV-7, HAdV-1, and HAdV-2, have previously been reported as potential pathogens associated with HAdV hepatitis in immunocompromised patients. However, few HAdV-related hepatitis cases have been reported in China to date., Conclusions: There are no systematic surveillance and clinical studies on HAdV hepatitis in China. Therefore, it is imperative to establish a nationwide HAdV virological surveillance system to collect relevant clinical, epidemiological and virological surveillance data and risk factor information as soon as possible to assess the potential risk of HAdV hepatitis among children., (© 2022. The Author(s).)

Background: Human adenovirus (HAdV) infection can cause a variety of diseases. It is a major pathogen of pediatric acute respiratory tract infections (ARIs) and can be life-threatening in younger children. We described the epidemiology and subtypes shifting of HAdV among children with ARI in Guangzhou, China., Methods: We conducted a retrospective study of 161,079 children diagnosed with acute respiratory illness at the Guangzhou Women and Children's Medical Center between 2010 and 2021. HAdV specimens were detected by real-time PCR and the hexon gene was used for phylogenetic analysis., Results: Before the COVID-19 outbreak in Guangzhou, the annual frequency of adenovirus infection detected during this period ranged from 3.92% to 13.58%, with an epidemic peak every four to five years. HAdV demonstrated a clear seasonal distribution, with the lowest positivity in March and peaking during summer (July or August) every year. A significant increase in HAdV cases was recorded for 2018 and 2019, which coincided with a shift in the dominant HAdV subtype from HAdV-3 to HAdV-7. The latter was associated with a more severe disease compared to HAdV-3. The average mortality proportion for children infected with HAdV from 2016 to 2019 was 0.38% but increased to 20% in severe cases. After COVID-19 emerged, HAdV cases dropped to 2.68%, suggesting that non-pharmaceutical interventions probably reduced the transmission of HAdV in the community., Conclusion: Our study provides the foundation for the understanding of the epidemiology of HAdV and its associated risks in children in Southern China., (© 2022. The Author(s).)

Known genetic variation, in conjunction with post-PCR melting curve analysis, can be leveraged to provide increased taxonomic detail for pathogen identification in commercial molecular diagnostic tests. Increased taxonomic detail may be used by clinicians and public health decision-makers to observe circulation patterns, monitor for outbreaks, and inform testing practices. We propose a method for expanding the taxonomic resolution of PCR diagnostic systems by incorporating a priori knowledge of assay design and sequence information into a genotyping classification model. For multiplexed PCR systems, this framework is generalized to incorporate information from multiple assays to increase classification accuracy. An illustrative hierarchical classification model for human adenovirus (HAdV) species was developed and demonstrated ~95% cross-validated accuracy on a labeled dataset. The model was then applied to a near-real-time surveillance dataset in which deidentified adenovirus detected patient test data from 2018 through 2021 were classified into one of six adenovirus species. These results show a marked change in both the predicted prevalence for HAdV and the species makeup with the onset of the COVID-19 pandemic. HAdV-B decreased from a pre-pandemic predicted prevalence of up to 40% to less than 5% in 2021, while HAdV-A and HAdV-F species both increased in predicted prevalence.

Human adenovirus (HAdV) is a common virus, but the infections it causes are relatively uncommon. At the same time, the methods for the detection of HAdV are varied, among which viral culture is still the gold standard. HAdV infection is usually self-limited but can also cause clinically symptomatic in lots of organs and tissues, of which human adenovirus pneumonia is the most common. In contrast, human adenovirus hepatitis is rarely reported. However, HAdV hepatitis has a high fatality rate once it occurs, especially in immunocompromised patients. Although human adenovirus hepatitis has some pathological and imaging features, its clinical symptoms are not typical. Therefore, HAdV hepatitis is not easy to be found in the clinic. There are kinds of treatments to treat this disease, but few are absolutely effective. In view of the above reasons, HAdV hepatitis is a disease that is difficult to be found in time. We reviewed and summarized the previously reported cases, hoping to bring some relatively common characteristics to clinicians, so as to facilitate early detection, early diagnosis, and early treatment of patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zheng, Wang, Rong, Wang and Huang.)

Human adenoviruses can cause infections at any age but most commonly in pediatric population, especially in young children and infants. By the time of 10 years old, most children have had at least one episode of adenovirus infection. Adenoviruses can cause many symptoms similar to common cold, including rhinorrhea, fever, cough, and sore throat. Lower respiratory infections such as bronchitis, bronchiolitis, and pneumonia can be severe and even fatal. Other diseases such as conjunctivitis, gastroenteritis, cystitis, myocarditis, cardiomyopathy, and meningoencephalitis can also be associated with adenovirus infections. A variety of recent advancement of structural and molecular biology methods have revamped the taxonomy of adenoviruses and furthered our understanding of the diversity of related clinical diseases. Because of the wide spectrum and complexity of diseases associated with human adenovirus infections, the scope of this review is limited to basic virology and epidemiology of adenoviruses with a main focus on the clinico-pathologic correlation. Clinical manifestations and pathology of any infectious disease are always related; therefore, it is logical to review clinico-pathologic correlation within the specific disease entity caused by adenoviruses to better understand this common viral infection in pediatric population., Competing Interests: Conflicts of interest The author declares no conflicts of interest. Some of the work described in this manuscript was done when the author was working as a medical officer at Infectious Diseases Pathology Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA., (Copyright © 2021 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Objective: Approximately 1 million adenovirus immunochromatography (IC) kits are annually used in Japan. However, no practical strategies have been developed regarding their use for detecting adenovirus. The present study aims to verify the usefulness of clinical manifestations in making decisions regarding the use of adenovirus IC kits for children with upper respiratory infections (URI)., Methods: The medical records of 825 pediatric cases tested by IC kits for adenovirus were extracted from clinical laboratory department database over a 3-year period at our hospital. Among them, 585 patients were suspected adenovirus URI, and their clinical manifestations were reviewed. After data cleaning, 10 types of clinical manifestations were statistically analyzed between adenovirus IC kit-positive and -negative groups. Multivariate analysis was performed to select significant clinical manifestations using adenovirus IC kit positivity as the objective variable., Results: Among 585 pediatric patients, the cases of 420 patients, with suitable data for whom no other pathogen was detected, were reviewed. Adenovirus was detected in 86 cases. Multivariate analysis identified a significant difference for three clinical manifestations: (1) fever ≥ 39.0°C, (2) rhinorrhea, and (3) tonsillar exudate. The negativity rate for the IC kit was 90% when none of the three manifestations was observed., Conclusions: The results suggested that IC kits for adenovirus tend to give negative results in cases that lack all the three above mentioned clinical manifestations., (© 2019 Wiley Periodicals, Inc.)

Purpose: To determine the characteristics of conjunctivitis associated with human adenovirus E4 (AdV E4)., Methods: Samples and outcomes from 500 patients with conjunctivitis were obtained from the NVC-422 randomized controlled clinical trial comparing auriclosene to placebo. Molecular typing identified 36 cases associated with AdV E4. Signs and symptoms at presentation and at the day 18 endpoint were compared with the larger cohort of 262 subjects with conjunctivitis caused by due to AdV D8. Full viral genomes of 22 AdV E4 isolates were reconstructed., Results: AdV E4 was the most frequently identified adenoviral type in conjunctivitis cases from the United States. Signs and symptoms at presentation were comparable to those associated with AdV D8. Viral load at presentation was comparable between groups but resolution was more rapid in the AdV E4 group. Clinical signs were fully resolved by day 18 in 26 of 36 (72%) patients with AdV E4. Subepithelial infiltrates developed in 12 of 36 (33%) patients with AdV E4 compared with 98 of 215 (45%) patients with AdV D8 (P = .0001). One hundred twenty-four polymorphisms were observed among 22 whole viral genome sequences, which clustered into 3 clades. Patients in each clade developed subepithelial infiltrates. Neither single nucleotide polymorphism analysis nor machine learning approaches identified specific sequence features predictive of presenting signs or outcome., Conclusions: AdV E4 conjunctivitis may be indistinguishable at presentation from AdV D8-associated disease. Resolution of viral load for AdV E4 appears more rapid than for AdV D8, and the risk for subepithelial infiltrates appears lower. Multiple substrains of AdV E4 are in circulation but all appeared equivalently pathogenic for conjunctivitis. NOTE: Publication of this article is sponsored by the American Ophthalmological Society., (Copyright © 2021. Published by Elsevier Inc.)

Background: HAdV is one of the common pathogens in hospitalized children with acute respiratory infections (ARIs). We aim to describe the clinical and laboratory features, epidemiological characteristics, and HAdV species and/or types of inpatients with HAdV respiratory infections., Methods: Respiratory samples were gathered from inpatients diagnosed ARIs in Children's Hospital, Zhejiang University School of Medicine, and were detected by using Direct Immunofluorescence Assay from 2018 to 2019. PCR amplification and sequencing of the hypervariable zone of hexon gene were used for genotyping. The clinical and laboratory features, and HAdV genotyping, and epidemiological characteristic analysis were retrospectively performed., Results: Of 7072 samples collected, 488 were identified as HAdV-positive. The overall detection rate was 6.9%. The peaked detection rate was 14.1% in January 2019. HAdV-positive cases with ARIs mainly appeared in winter. The detection rate was highest among children between 6 months and 2 years (8.7%, 123/1408). Clinical diagnosis included pneumonia (70.3%, 343/488), bronchitis (7.0%, 34/488) and acute upper respiratory tract infection (22.7%, 111/488). The common clinical manifestations were fever (93.4%, 456/488), cough (94.7%, 462/488), wheezing (26.2%, 128/488), and shortness of breath (14.8%, 72/488). 213 (43.6%) cases had co-infection and 138 (28.3%) cases had extrapulmonary symptoms. 96(19.7%) cases had intrapulmonary and intrathoracic complications.78 (16.0%) had an underlying condition, most of which were congenital heart diseases (20.5%, 16/78). The proportions of hyperpyrexia, duration of fever > 10 days, severe pneumonia, and wheezing in the co-infection group were remarkably higher than those in HAdV single-infection group (all p < 0.05). The proportions of duration of hospitalization, duration of fever > 10 days, wheezing, shortness of breath, change in level of consciousness, serosal fluids, extrapulmonary symptoms, co-infections and underlying diseases were significantly higher in severe pneumonia group than those in the mild pneumonia group (all p < 0.05). Four HAdV species were successfully identified in 155 cases and presented by 8 genotypes. HAdV-B3 (56.1%, 87/155) and HAdV -B7 (31.0%, 48/155) were the most predominant detected types and occurred commonly in different severity groups (p = 0.000), while, HAdV-B55 was detected only in the severe group. HAdV-B7's detection rate in the severe pneumonia group was significantly higher than the non-severe pneumonia group., Conclusion: HAdV detection rate is related to age and season. Bronchopneumonia accounts for about 70% HAdV-positive inpatients. The common clinical manifestations include hyperpyrexia, cough, wheezing, and shortness of breath. HAdV-B3 and HAdV-B7 are the most common types in children diagnosed with respiration infections., (© 2021. The Author(s).)

To understand the clinical course of human adenoviral (HAdV) conjunctivitis and establish a better treatment regimen, 38 eyes of 19 patients with HAdV-54 conjunctivitis for less than one week from onset were evaluated for clinical signs and symptoms and DNA copy numbers. A viral load of 10 4 -10 5 is required to develop symptoms of HAdV conjunctivitis, as symptoms were present in eyes with viral loads of ≥10 4 at least once during the course. Next, it was observed that asymptomatic infections in the contralateral eyes are common, as the virus was detected in most eyes that did not develop conjunctivitis. Furthermore, there was no rapid decrease in the viral load in healed eyes; on the contrary, the viral load in the healed eyes on day 15 was significantly higher than that in the unhealed eyes. This was likely due to corticosteroid instillation, which rapidly alleviated symptoms but prolonged the duration of viral shedding. Recently, combination treatment with iodine and corticosteroids has been recommended for HAdV conjunctivitis. Assessing changes in the viral load and clinical symptoms would be helpful to better understand the clinical course of this disease.

Purpose : To examine the effects of treatments performed on children with adenoviral conjunctivitis. Methods : 50 children with Adenoviral keratoconjunctivitis (AK) were evaluated. Patients were divided into four groups according to the medical treatment agents that were used previously. AK symptoms were clinically scored and analyzed. The diagnosis of all children was confirmed by an in-office lateral flow immunoassay. Results : Fifty patients with AK were included in the study. 24 (48%) were female and 26 (52%) were male. The mean age was 12.88 ± 2.66 (8-17). In PVP-I groups clinical findings shows faster improvement than other groups ( p < .05). Conclusions : Conjunctival irrigation with 2.5% PVP-I is very effective for the treatment of adenoviral conjunctivitis in childhood. Ganciclovir ophthalmic gel 0.15% increases the effect of 2.5% PVP-I on AK, but this was not statistically significant.

Human Adenoviruses (HAdV) are known to be potentially associated with strong inflammatory responses and morbidity in pediatric patients. Although most of the primary infections are self-limiting, the severity of clinical presentation, the elevation of the white blood cell count and inflammatory markers often mimic a bacterial infection and lead to an inappropriate use of antibiotics. In infections caused by HAdV, rapid antigen detection kits are advisable but not employed routinely; costs and feasibility of rapid syndromic molecular diagnosis may limit its use in the in-hospital setting; lymphocyte cultures and two-sampled serology are time consuming and impractical when considering the use of antibiotics. In this review, we aim to describe the principal diagnostic tools and the immune response in HAdV infections and evaluate whether markers based on the response of the host may help early recognition of HAdV and avoid inappropriate antimicrobial prescriptions in acute airway infections.

Three human adenovirus (HAdV) genotypes, HAdV-7, HAdV-14, and HAdV-55, emerged as the most prevalent variants in China over the past decade and caused both sporadic, fatal cases and frequent, large outbreaks. Early diagnosis is essential to control infections and endemics. Here, we established a loop-mediated isothermal amplification (LAMP) assay coupled with an instrument-free nucleic acid extraction device recently developed by our group; the assay could detect all the 3 prevalent HAdV genotypes. Specificity analysis showed no cross-reactivity with other common respiratory pathogens and the analytical sensitivity was as low as 10 copies/μL. All detection steps could be completed within 1 hour. The assay's performance was evaluated using clinical samples and compared with the gold standard RT-PCR method, showing highly consistent results. The LAMP assay developed here could be readily used in basic laboratory facilities and with minimal DNA extraction equipment, and as a reliable screening test in a resource-limited setting., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The rise in human adenovirus (HAdV) infections poses a serious challenge to public health in China. Real-time (RT) sequencing provides solutions for achieving rapid pathogen identification during outbreaks, whereas high-throughput sequencing yields higher sequence accuracy. In the present study, we report the outcomes of applying nanopore and BGI platforms in the identification and genomic analysis of an HAdV outbreak in Hubei province, China in May of 2019. A mixed sample of nine nasopharyngeal swabs and one single sample were submitted to direct nanopore sequencing (MinION device), generating their first HAdV-55 reads within 13 and 20 min, respectively. The sequences were confirmed by RT-polymerase chain reaction (PCR). Ten HAdV-positive samples were further sequenced using next-generation high-throughput sequencing (BGISEQ-500 device). Phylogenetic analysis revealed that the outbreak strain had a close genetic relation to strains isolated in Sichuan province. Metagenomic analysis showed that HAdV-55 was not a dominant species in samples from which the whole HAdV-55 genome could not be assembled. The present results highlight the value of combining sequencing platforms and using mixed samples for nucleic acid enrichment in pathogen detection of infectious disease outbreaks., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Adenovirus infections are prevalent in children. They usually cause a mild self-limited disease. However, this infection can be associated with considerable morbidity and mortality in specific populations, especially among immunocompromised children. Children with Down syndrome are susceptible to a higher frequency and increased severity of viral infections. Little is known about the severity and clinical course of adenovirus infections in children with Down syndrome., Objectives: To characterize hospitalized children diagnosed with Down syndrome and presenting with adenovirus infection., Methods: We performed a retrospective review of children admitted with adenovirus from January 2005 to August 2014 from a single tertiary pediatric medical center in Israel. Data were compared between patients with and without Down syndrome., Results: Among the 486 hospitalized children with adenoviral infection, 11 (2.28%) were diagnosed with Down syndrome. We found that children with Down syndrome were more likely to experience a higher incidence of complications (18.2% vs. 2.4%, P = 0.008), a higher rate of admissions to the intensive care unit (36.4% vs. 2.4%, P < 0.001), and more prolonged hospitalizations (17 ± 15.9 days compared to 4.46 ± 3.16, P = 0.025)., Conclusions: Children with Down syndrome who were hospitalized with adenovirus infection represent a high-risk group and warrant close monitoring. If a vaccine for adenovirus becomes available, children with Down syndrome should be considered as candidates.

Human adenoviruses (HAdVs) are associated with respiratory infection in the human population worldwide, but HAdV is underreported and less studied than other respiratory viruses. We investigated HAdV in patients with respiratory infection in Rio Grande do Sul (RS), Brazil, between 2004 and 2018. The frequency and seasonality of HAdV, clinical symptoms and underlying diseases were analysed. Respiratory samples from outpatients with acute respiratory illness (ARI) who attended sentinel units and from inpatients with severe acute respiratory infection (SARI) were collected for HAdV detection by immunofluorescence assay; demographic and clinical data were analysed. In total, 43,514 cases of respiratory infection were analysed, of which 8,901 were ARI (20.5%), and 34,613 (79.5%) were SARI. Respiratory viruses were detected in 35.8% of the cases. The frequency of HAdV in relation to respiratory viruses was 2.8%. HAdV circulated year-round, with higher frequency during winter and early spring; increases in the average monthly temperature were associated with decreases in HAdV infections (p = 0.013). Most hospitalized patients with HAdV were male (p = 0.003). HAdV infection showed association with age (p < 0.001), and children between 1 and 5 years old accounted for 30.8% of the outpatients, whereas among cases of SARI, 88.2% were paediatric patients. Among inpatients with HAdV, 3% died, and of these, the majority had at least one underlying condition, such as cardiopathy and immunosuppression. HAdV infection of the respiratory tract causes morbidity and mortality, and individuals with heart diseases and the immunocompromised are at higher risk of fatality., (© 2020 John Wiley & Sons Ltd.)

Background: Human adenovirus (HAdV)-D56 was first described in 2011 by genomics analysis of a strain isolated in France in 2008 from a fatal case of neonatal infection. Since then, it has been reported in cases of keratoconjunctivitis and male urethritis. Three epidemiologically unrelated fatal cases of neonatal sepsis associated with infection by HAdV-D strains with a similar genetic makeup were documented in the United States between 2014 and 2020., Methods: Whole genome sequences were obtained for the isolated strains, and genomics analyses were conducted to compare them to phylogenetically related HAdV-D genomic sequences available in GenBank., Results: The three new US strains were indistinguishable by in silico restriction enzyme analysis. Their genome sequences were 99.9% identical to one another and to the prototype strain isolated in 2008 from a similar context of disease. The phylogenetic reconstruction revealed a highly supported clustering of all HAdV-D56 strains isolated in various countries since 1982. Our comparison to serologically intermediate strains 15/H9 described in the literature indicated that HAdV-D56-like viruses have circulated worldwide since the late 1950s., Conclusion: As with other HAdV-D genotypes with the ability to infect ocular and genital mucosae, the risk of severe prenatal or perinatal HAdV-D56 infection must be considered.

Abstract: To investigate the epidemiology and factors associated with the severity of viral acute lower respiratory infection (ALRI) in children hospitalized in Manaus, Amazonas, in 2017 to 2018.Retrospective cohort study of children hospitalized at the Hospital and Emergency Room Delphina Rinaldi Abdel Aziz, in Manaus, from April 01, 2017 to August 31, 2018, with a clinical diagnosis of ALRI and nasopharyngeal aspirates positive for at least 1 respiratory virus.One hundred forty-six children aged 0.2 to 66 months (median 7 months) were included. Patients were divided into 2 groups according to the disease severity classified by an adapted Walsh et al score: moderate disease, score 0-4, n = 66 (45.2%) and severe disease, score 5-7, n = 80 (54.8%). A greater number of viral ALRI cases were observed in the rainiest months. Respiratory syncytial virus was the most prevalent (n = 103, 70.3%), followed by metapneumovirus (n = 24, 16.4%), influenza virus (n = 17, 11.6%), parainfluenza virus (n = 11, 7.5%), and adenovirus (n = 4, 2.7%). Co-detections of 2 to 3 viruses were found in 12 (8.2%) patients. The presence of viral coinfection was an independent risk factor for disease severity (adjusted relative risk [RR] 1.53; 95% CI 1.10-2.14). Twelve patients (8.2%) died, all with severe disease. Risk factors for death were shock (adjusted RR 10.09; 95% CI 2.31-43.90) and need for vasoactive drugs (adjusted RR 10.63; 95% CI 2.44-46.31).There was a higher incidence of viral ALRI in Manaus in the rainy season. Respiratory syncytial virus was the most prevalent virus. The presence of viral coinfection was an independent risk factor for disease severity., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Importance: Adenoviral conjunctivitis is highly contagious, can be associated with systemic infections, and can cause chronic visual impairment. It accounts for a large proportion of acute conjunctivitis. Outbreaks of epidemic keratoconjunctivitis (EKC) are costly in terms of productivity loss from work furloughs and spread to patients and have resulted in clinic and departmental closures., Objective: To examine the institutional cost savings of a policy to diagnose adenoviral conjunctivitis and triage and furlough medical center employees with this condition to prevent outbreaks., Design, Setting, and Participants: This quality improvement study assessed Johns Hopkins Medicine employees with red eye from November 1, 2011, through October 31, 2018, who were triaged at the occupational health clinic whose conditions were diagnosed using polymerase chain reaction (PCR) validated for adenoviral conjunctivitis., Interventions: Only employees with positive PCR test results were furloughed, with furlough length tailored to subtype (a minimum of 2 weeks for EKC and 1 week otherwise)., Main Outcomes and Measures: Total number of furloughs avoided and cost savings associated with reducing unnecessary furloughs., Results: Of 2142 employees with red eye, 1520 (71.0%) underwent PCR testing; 130 (8.6%) had positive adenoviral PCR test results, of whom 41 (31.5%) had EKC. Furloughing 130 employees with positive PCR test results vs furloughing all 1520 employees clinically suspected of having adenoviral conjunctivitis represented an estimated annual savings of $442 073, or $3 094 511 during 7 years. The cost of performing PCR on employees suspected of having adenoviral conjunctivitis was 5.0% of the cost associated with furloughing all employees with red eye. No outbreaks occurred., Conclusions and Relevance: In this quality improvement study, this policy, notable for development and use of PCR for adenoviral conjunctivitis on a large scale, resulted in substantial cost savings from fewer work furloughs compared with the number of employees who would have been furloughed based on clinical diagnosis. These results may provide impetus for policy adoption by other institutions and for development of a rapid, sensitive, and specific diagnostic test for adenoviral conjunctivitis.

Adenoviruses are emerging as important viral pathogens in immunocompromised patients due to immunodeficiency diseases and recently hematopoietic stem cell and solid organ transplant recipients, impacting morbidity and even mortality. Immunocompromised children are prone to respiratory infection, due to alterations in their immune system. When confronted with diseases involving the pleural effusions, such as viral infections, the diagnostic problem becomes more complex and special effort is needed to recognize and characterize them accurately and to differentiate them from other pathologies such as malignancies. However, cytology of adenoviral infection in pleural effusions has not been reported before. We report a case of an adenovirus infection of the pleural effusion which included lymphocytosis associated with background atypical cells showing a cytopathic effect (cytoplasmic viral particles). The differential diagnosis included lymphoma and infections. Immunohistochemical stain for adenovirus was positive and confirmed by molecular studies. Usually in viral infections there are cytopathic changes due to viral particles affecting epithelial cells but this case is unique as the viral particles were identified in macrophages. We discuss the significance of such infection in comparison with other viral changes indigenous to the pleural effusions, which could also occur in such specimens., (© 2021 Wiley Periodicals LLC.)

Purpose: To analyze the epidemiologic characteristics of an outbreak of human adenovirus type 54 (HAdV-54) on Oki Island, Shimane Prefecture, Japan, in 2017 and to assess the effectiveness of a compartmentalization method in controlling the incidence and spread., Study Design: Retrospective cohort study., Methods: The infection was diagnosed in 136 individuals, and typing was confirmed by PCR and direct sequencing. The epidemiologic characteristics of the disease including the infection rate, incubation period, and basic reproductive number (R 0 ), ie, number of cases directly infected by an infectious patient during the course of the disease, were investigated. The effectiveness of compartmentalization for infection control was determined by simulating the outbreak using the Susceptible-Exposed-Infectious-Recovered (SEIR) model., Results: The majority of the HAdV-54-infected individuals were the children of 3 nursery schools (A, B, and C) and their parents on Oki Island. The infection rates in the 3 schools were 13.2%, 16.9%, and 17.2%, respectively. The one class of school B without the index case was initially compartmentalized, and the infection rate in this compartment was 0%. The incubation period was calculated to be 9.3 ± 3.5 days, and the disease duration, 13.0 ± 5.4 days. The R 0 was 1.43. Using these parameters, a SEIR model was constructed. The SEIR model well predicted the daily incidence of infection and indicated that the compartmentalization method provides effective reduction in the incidence of the infection, with much earlier control., Conclusions: The compartmentalization method is effective to control HAdV-54 outbreaks.

A subset of patients with Covid-19 presents with negative RT-PCR screening but suspect CT findings. Using four commercially available anti-SARS-CoV-2 IgG immuno-assays, we found this subset constituted 9.2% of all consecutively admitted outpatients with Covid-19 in our hospital. Clinical specificity for Covid-19 of some N protein-based immuno-assays was suboptimal, as positive results were observed in control patients with recent common human coronavirus, influenza B and adenovirus infections.